We have assembled an outstanding group of scientists to work on the regeneration of the tooth and its supporting tissues. This ambitious project will require novel scientific approaches and strong collaborative interactions as high performance teams among scientific disciplines that tend to work in isolation. Scientific expertise from molecular biology, computer sciences, genetics, chemistry, physics, materials sciences and engineering are required. We use the diverse skills of our scientific team to perform a SWOT analysis to identify the Strengths, Weaknesses, Opportunities and Threats to the goal of tooth regeneration. We will create a blueprint for a human tooth that includes the materials properties, gene expression profiles, matrix molecules, and signaling pathways that draws from our existing knowledge of the development and evolution of teeth. This blueprint is used to provide the design specifics for two unique, but complementary roads to engineer a replacement. A biological approach using stem- and/or genetically engineered cells, signaling molecules and nanofabricated extracellular matrix molecules to direct regeneration is envisioned. Alternatively, biomimetic inspired molecules are used with nano- and micro technology tools to create materials that replace dental tissues. The SWOT analysis will identify gaps in knowledge or technology that impede our progress and the means to obviate them. We will create a Concept Development Plan that details and prioritizes specific processes, procedures and projects to achieve tooth regeneration and outlines the organizational structure, including the environment for promoting interdisciplinary and collaborative basic and translational applied research needed for the U54 program. [unreadable] [unreadable] [unreadable]